ROPN1L

Summary

ROPN1L (rhophilin associated tail protein 1 like, HGNC:24060) is a protein-coding gene on chromosome 5p15.2, encoding Ropporin-1-like protein (Q96C74). Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.

This gene encodes a member of the ropporin family. The encoded protein is present in sperm and interacts with A-kinase anchoring protein, AKAP3, through the amphipathic helix region of AKAP3. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 83853 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_031916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24060
Approved symbol	ROPN1L
Name	rhophilin associated tail protein 1 like
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	ASP, FLJ25776, RSPH11, RP11-1C1.7, TCONS_00009352
Ensembl gene	ENSG00000145491
Ensembl biotype	protein_coding
OMIM	611756
Entrez	83853

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding_CDS_not_defined, 2 protein_coding, 2 retained_intron

ENST00000274134, ENST00000416930, ENST00000503804, ENST00000510520, ENST00000512022, ENST00000515762, ENST00000718289, ENST00000718290, ENST00000718291, ENST00000718292

RefSeq mRNA: 2 — MANE Select: NM_031916 NM_001201466, NM_031916

CCDS: CCDS3879

Canonical transcript exons

ENST00000274134 — 5 exons

Exon	Start	End
ENSE00000996119	10464848	10465026
ENSE00003528814	10449952	10450113
ENSE00003594769	10448260	10448383
ENSE00003664550	10461184	10461359
ENSE00004034651	10441879	10442298

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 98.95.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8909 / max 872.8494, expressed in 562 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55706	2.1190	543
55707	0.4568	48
55708	0.2756	6
55710	0.0278	5
55709	0.0118	4

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.95	gold quality
right testis	UBERON:0004534	98.84	gold quality
bronchial epithelial cell	CL:0002328	98.83	gold quality
adult organism	UBERON:0007023	98.81	gold quality
sperm	CL:0000019	98.50	gold quality
bronchus	UBERON:0002185	98.02	gold quality
right uterine tube	UBERON:0001302	97.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.98	gold quality
testis	UBERON:0000473	95.74	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.83	gold quality
epithelium of nasopharynx	UBERON:0001951	90.09	gold quality
nasal cavity epithelium	UBERON:0005384	87.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.58	gold quality
nasal cavity mucosa	UBERON:0001826	85.84	gold quality
blood	UBERON:0000178	85.04	gold quality
fallopian tube	UBERON:0003889	84.17	gold quality
oviduct epithelium	UBERON:0004804	83.47	gold quality
trachea	UBERON:0003126	80.68	gold quality
right lung	UBERON:0002167	78.24	gold quality
bone marrow	UBERON:0002371	73.83	gold quality
spleen	UBERON:0002106	72.59	gold quality
granulocyte	CL:0000094	72.36	gold quality
left uterine tube	UBERON:0001303	71.18	gold quality
caput epididymis	UBERON:0004358	69.19	gold quality
upper lobe of left lung	UBERON:0008952	69.04	gold quality
leukocyte	CL:0000738	67.45	gold quality
monocyte	CL:0000576	66.80	gold quality
upper lobe of lung	UBERON:0008948	66.72	gold quality
hypothalamus	UBERON:0001898	66.57	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	805.43
E-GEOD-134144	yes	29.40
E-MTAB-10287	yes	27.01
E-HCAD-1	yes	26.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Single nucleotide polymorphisms in ROPN1L gene is associated with breast cancer. (PMID:21424380)
• Sp17 and ASP cancer/testis antigens were found in ciliated cells of four ciliated hepatic foregut cysts (CHFCs). Further characterization of Sp17 and ASP in patients with CHFCs may provide significant clues for understanding the molecular mechanisms underlying their predisposition to develop squamous cell carcinomas. (PMID:25600306)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ropn1l	ENSDARG00000058370
mus_musculus	Ropn1l	ENSMUSG00000022236
rattus_norvegicus	Ropn1l	ENSRNOG00000042781

Paralogs (2): ROPN1 (ENSG00000065371), ROPN1B (ENSG00000114547)

Protein

Protein identifiers

Ropporin-1-like protein — Q96C74 (reviewed: Q96C74)

Alternative names: AKAP-associated sperm protein

All UniProt accessions (1): Q96C74

UniProt curated annotations — full annotation on UniProt →

Function. Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. Important for male fertility. With ROPN1, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.

Subunit / interactions. Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB. Interacts with FSCB; the interaction increases upon spermatozoa capacitation conditions. May interact with AKAP3. Interacts with CFAP61.

Subcellular location. Cell projection. Cilium. Flagellum.

Post-translational modifications. Sumoylated, sumoylation decreases upon spermatozoa capacitation conditions.

Similarity. Belongs to the ropporin family.

RefSeq proteins (2): NP_001188395, NP_114122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR047844	ROP_DD	Domain

UniProt features (5 total): sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C74-F1	85.98	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, MARTINEZ_RB1_TARGETS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM

GO Biological Process (4): epithelial cilium movement involved in extracellular fluid movement (GO:0003351), flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240), cilium movement (GO:0003341)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (11): radial spoke (GO:0001534), extracellular region (GO:0005576), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cilium (GO:0005929), motile cilium (GO:0031514), ciliary transition zone (GO:0035869), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
sperm flagellum	3
cilium	2
cilium movement	1
extracellular transport	1
microtubule-based transport	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
microtubule-based movement	1
protein binding	1
binding	1
axoneme	1
protein-containing complex	1
nuclear lumen	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROPN1L	AKAP3	O75969	924
ROPN1L	CABYR	O75952	917
ROPN1L	SPA17	Q15506	905
ROPN1L	RHPN1	Q8TCX5	853
ROPN1L	CYREN	Q9BWK5	637
ROPN1L	SPATA16	Q9BXB7	593
ROPN1L	FSCB	Q5H9T9	589
ROPN1L	GARIN2	Q8N9W8	543
ROPN1L	PRKACG	P22612	534
ROPN1L	RNF17	Q9BXT8	531
ROPN1L	PRKACA	P17612	522
ROPN1L	PRKACB	P22694	521
ROPN1L	DMRT1	Q9Y5R6	508
ROPN1L	CATIP	Q7Z7H3	505
ROPN1L	AKAP1	Q92667	503

IntAct

31 interactions, top by confidence:

A	B	Type	Score
RSPH3	ROPN1L	psi-mi:“MI:0915”(physical association)	0.780
ROPN1L	RSPH3	psi-mi:“MI:0915”(physical association)	0.780
ROPN1L	SPA17	psi-mi:“MI:0914”(association)	0.740
SPA17	ROPN1L	psi-mi:“MI:0915”(physical association)	0.740
AKAP14	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
AKAP7	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
BEX2	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
AKAP5	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
ROPN1L	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
ROPN1L	BEX2	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	UBB	psi-mi:“MI:0914”(association)	0.530
AKAP3	ROPN1L	psi-mi:“MI:0915”(physical association)	0.370
ROPN1L	CD74	psi-mi:“MI:0914”(association)	0.350
ROPN1L	RSPH3	psi-mi:“MI:0915”(physical association)	0.000
SPA17	ROPN1L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): RSPH3 (Two-hybrid), AKAP9 (Affinity Capture-MS), SPA17 (Affinity Capture-MS), SPA17 (Affinity Capture-MS), ROPN1L (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), ROPN1L (Two-hybrid), ROPN1L (Two-hybrid), ROPN1L (Two-hybrid), ROPN1L (Two-hybrid), ROPN1L (Two-hybrid), AKAP5 (Two-hybrid), AKAP14 (Two-hybrid), ROPN1L (Two-hybrid), CD74 (Affinity Capture-MS)

ESM2 similar proteins: A0AVX7, A2VEI2, F4J0W4, O43745, O70200, O73761, O73762, P04354, P04467, P05937, P07171, P12658, P22728, P41044, P43080, P43081, P46065, P51177, P55008, P61022, P61023, P79880, P81076, Q0V9B1, Q1LWZ0, Q298L5, Q3KQ77, Q3SYS6, Q3T024, Q4R760, Q4V7T8, Q5R4V1, Q5R7F0, Q5TM25, Q5U554, Q5ZM44, Q6P8Y1, Q810D1, Q8IMX7, Q8R426

Diamond homologs: Q3T024, Q3T064, Q4KLL5, Q4R6C5, Q4R760, Q4V7T8, Q66IC9, Q96C74, Q9BZX4, Q9EQ00, Q9ESG2, Q9HAT0, P86196, P13861

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

807 predictions. Top by Δscore:

Variant	Effect	Δscore
5:10442294:GCGGG:G	donor_gain	1.0000
5:10442295:CGGGG:C	donor_loss	1.0000
5:10442296:GGG:G	donor_gain	1.0000
5:10442297:GG:G	donor_gain	1.0000
5:10442297:GGG:G	donor_gain	1.0000
5:10442298:GG:G	donor_gain	1.0000
5:10442299:G:GC	donor_loss	1.0000
5:10442300:T:G	donor_loss	1.0000
5:10449946:A:AG	acceptor_gain	1.0000
5:10449947:A:G	acceptor_gain	1.0000
5:10449947:AACAG:A	acceptor_loss	1.0000
5:10449950:A:AG	acceptor_gain	1.0000
5:10449950:AG:A	acceptor_loss	1.0000
5:10449950:AGT:A	acceptor_gain	1.0000
5:10449951:G:GA	acceptor_gain	1.0000
5:10449951:GT:G	acceptor_gain	1.0000
5:10449951:GTG:G	acceptor_gain	1.0000
5:10449951:GTGT:G	acceptor_gain	1.0000
5:10449951:GTGTC:G	acceptor_gain	1.0000
5:10450109:GTGGG:G	donor_gain	1.0000
5:10450111:GGG:G	donor_gain	1.0000
5:10450111:GGGGT:G	donor_loss	1.0000
5:10450112:GGG:G	donor_gain	1.0000
5:10450112:GGGT:G	donor_loss	1.0000
5:10450114:G:GC	donor_loss	1.0000
5:10450114:G:GG	donor_gain	1.0000
5:10450115:T:G	donor_loss	1.0000
5:10461166:T:TA	acceptor_gain	1.0000
5:10461170:T:TA	acceptor_gain	1.0000
5:10461172:T:TA	acceptor_gain	1.0000

AlphaMissense

1506 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:10442243:T:C	F26L	0.997
5:10442245:C:A	F26L	0.997
5:10442245:C:G	F26L	0.997
5:10442288:T:A	W41R	0.997
5:10442288:T:C	W41R	0.997
5:10442256:C:A	A30D	0.996
5:10442290:G:C	W41C	0.996
5:10442290:G:T	W41C	0.996
5:10449997:T:A	W101R	0.996
5:10449997:T:C	W101R	0.996
5:10442262:G:C	R32P	0.995
5:10448264:T:C	F46L	0.995
5:10448266:T:A	F46L	0.995
5:10448266:T:G	F46L	0.995
5:10442239:G:C	K24N	0.994
5:10442239:G:T	K24N	0.994
5:10442251:G:C	K28N	0.994
5:10442251:G:T	K28N	0.994
5:10442223:T:C	L19P	0.993
5:10442244:T:C	F26S	0.993
5:10442252:G:C	A29P	0.993
5:10450072:T:A	W126R	0.993
5:10450072:T:C	W126R	0.993
5:10442235:T:C	L23P	0.992
5:10442255:G:C	A30P	0.992
5:10448265:T:C	F46S	0.992
5:10442189:T:C	F8L	0.991
5:10442191:C:A	F8L	0.991
5:10442191:C:G	F8L	0.991
5:10442259:T:A	I31N	0.991

dbSNP variants (sampled 300 via entrez): RS1000179500 (5:10443393 C>T), RS1000301540 (5:10466655 C>T), RS1000330300 (5:10461853 C>G,T), RS1000346262 (5:10453344 G>A), RS1000374615 (5:10466432 C>A,T), RS1000401989 (5:10450486 A>G), RS1000530216 (5:10470515 G>C), RS1000553588 (5:10448102 G>A,C), RS1000640430 (5:10479550 C>T), RS1000778175 (5:10479236 C>G), RS1000779430 (5:10453600 T>C), RS1000796153 (5:10445099 T>C), RS1000933970 (5:10473274 A>C,G,T), RS1000955297 (5:10450749 C>A), RS1001046508 (5:10470256 T>C)

Disease associations

OMIM: gene MIM:611756 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001012_1	Breast cancer	2.000000e-06
GCST001448_2	Body mass index	1.000000e-06
GCST006053_2	Dermatomyositis or juvenile dermatomyositis	5.000000e-06
GCST006231_26	Mean arterial pressure	4.000000e-06
GCST006281_6	Coronary artery disease in type 1 diabetes	8.000000e-06
GCST008150_3	Triglyceride levels	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006340	mean arterial pressure
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	increases expression	1
Iron	decreases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	increases expression	1
Genistein	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.